An intensive care unit (ICU) stay is often a stressful and painful experience. Recent surveys indicate that 50–80% of patients experience pain during their ICU stay . Critically ill patients experience pain more readily than healthy subjects; a phenomenon known as hypernociception. The most painful experiences for ICU patients are endotracheal suctioning and being turned in bed. In addition, many patients have pain at rest without a noxious stimulus . This decreased threshold of pain in the ICU has been attributed to immobility and systemic inflammation. In addition to pain, ICU patients often suffer from stress, which has been frequently attributed to painful procedures. Other factors that may play a role in ICU stress include inability to communicate due to endotracheal intubation, interruption of sleep, hallucinations, and nightmares. This stressful experience is not without complications, as one retrospective study found that 25% of ICU patients with self-reported stressful experiences during their ICU stay, such as nightmares, anxiety, respiratory distress, or pain, showed symptoms of post-traumatic stress disorder four years later , thus, the importance of adequate analgesia and sedation to achieve patient comfort.
An intensive care unit (ICU) stay is often a stressful and painful experience. Recent surveys indicate that 50–80% of patients experience pain during their ICU stay [Reference Marino1]. Critically ill patients experience pain more readily than healthy subjects; a phenomenon known as hypernociception. The most painful experiences for ICU patients are endotracheal suctioning and being turned in bed. In addition, many patients have pain at rest without a noxious stimulus [Reference Marino1]. This decreased threshold of pain in the ICU has been attributed to immobility and systemic inflammation. In addition to pain, ICU patients often suffer from stress, which has been frequently attributed to painful procedures. Other factors that may play a role in ICU stress include inability to communicate due to endotracheal intubation, interruption of sleep, hallucinations, and nightmares. This stressful experience is not without complications, as one retrospective study found that 25% of ICU patients with self-reported stressful experiences during their ICU stay, such as nightmares, anxiety, respiratory distress, or pain, showed symptoms of post-traumatic stress disorder four years later [Reference Schelling, Stoll and Haller2], thus, the importance of adequate analgesia and sedation to achieve patient comfort.
The importance of providing such comfort has to be balanced with the need to minimize continuous deep sedation and paralysis, as the latter has been shown to improve outcome and decrease length of stay[Reference Kress, Pohlman, O’Connor and Hall3]. Sedatives have been questionably attributed to long-term cognitive decline as well. However, a recent large prospective cohort study of medical and surgical ICU patients who suffered respiratory failure or shock found no correlation between the use of sedatives and decline in neuropsychological examination at 3 and 12 months after an ICU stay [Reference Pandharipande, Girard and Jackson4]. In neurologically injured patients, one of the primary tenets of care is the capacity to perform repeated neurologic exams as the optimal means of assessing the patients’ condition. With respect to bedside evaluation and titration of sedation, the neurologically injured patient may indeed be the most difficult ICU population to manage [Reference Makii, Mirski and Lewin5]. Cognitive dysfunction leads to increased fear, restlessness, and agitation from the inability to understand one’s predicament. Yet even modest sedation may mask subtle neurologic deterioration, hence the need for close nursing, physician support and observation, and titrating medications as needed without impairing neurologic evaluation [Reference Mirski and Hemstreet6].
Patients with traumatic brain injury (TBI) constitute the hallmark brain disorder when discussing difficult sedation paradigms. They are often agitated and at risk of injury to self or the medical staff caring for them. Many TBI patients are also withdrawing from chronic alcohol and drug use, and this must be factored into the choice and duration of sedation [Reference Mirski and Hemstreet6].
Indications for Sedation
As discussed above, ICU patients often experience anxiety due to stressful events. Anxiety may coincide with motor signs known as agitation. This is often associated with alteration in mental status, known as delirium [Reference Marino1,Reference Barr, Fraser and Puntillo7]. The latter is important to recognize, as it may be a sign of an underlying systemic condition or neurologic dysfunction, including hypoxemia, hypercapnia, metabolic disturbances, infection, cerebral hypoperfusion or ischemia, and concomitant administration of psycho-active medications such as antidepressants, anticonvulsants, peptic ulcer prophylactics, and interactions with promotility agents or corticosteroids. In such a situation, the underlying pathology should be addressed first [Reference Barr, Fraser and Puntillo7].
After ruling out other etiologies, sedation may be initiated for goals of [Reference Marino1]:
Facilitating mechanical ventilation
Facilitating neurological exams
Avoiding deleterious changes in intracranial and cerebral perfusion pressures.
Sedation consists of anxiolysis, hypnosis, and amnesia [Reference Makii, Mirski and Lewin5,Reference Mirski and Hemstreet6]. The amnestic effect of the sedative regimen likely decreases long-term unpleasant psychiatric events. In neurologically ill patients, an ideal sedation regimen will either preserve the neurologic examination as required for constant clinical monitoring or has the potential to be discontinued with rapid return for an uncompromised examination. Preferred agents therefore should have rapid onset, short duration of action, and a large therapeutic window without significant hemodynamic effects [Reference Makii, Mirski and Lewin5,Reference Mirski and Hemstreet6,Reference Jacobi, Fraser and Coursin8]. Periodic interruption of sedative infusions and titration to the lowest effective dose are associated with shorter duration on mechanical ventilation, fewer tracheostomies, and shortened ICU stay [Reference Kress, Pohlman, O’Connor and Hall3].
Subjective Assessment of Sedation and Agitation
Frequent assessment of the degree of sedation or agitation may facilitate the titration of sedatives to predetermined endpoints. An ideal sedation scale should provide data that are simple to compute and record, accurately describe the degree of sedation or agitation within well-defined categories, guide the titration of therapy, and have validity and reliability in ICU patients [Reference Makii, Mirski and Lewin5,Reference Mirski and Hemstreet6] (see Figure 5.1).
Figure 5.1 Algorithm for the sedation and analgesia of mechanically ventilated patients. This algorithm is a general guideline for the use of analgesics and sedatives. Refer to the text for clinical and pharmacologic issues that dictate optimal drug selection, recommended assessment scales, and precautions for patient monitoring. Doses are approximate for a 70 kg adult. IVP = intravenous push [Reference Jacobi, Fraser and Coursin8].
A sedation goal or endpoint should be established and regularly redefined for each patient. Regular assessment and response to therapy should be systematically documented. The use of a validated sedation assessment scale is recommended (Table 5.1). The most commonly used sedation score is the RASS. The NICS is another score that may be easier to apply and communicate (Table 5.1)[Reference Mirski and Hemstreet6,Reference Mirski, LeDroux and Lewin9]. Objective measures of sedation using, for example, a bispectral index (BIS) monitor are not routinely used in the ICU.
|Richmond Agitation Sedation Scale (RASS) [Reference Barr, Fraser and Puntillo7]|
|+4 Combative||Overtly combative, violent, immediate danger to staff|
|+3 Very agitated||Pulls, removes tubes or catheters, aggressive|
|+2 Agitated||Frequent nonpurposeful movements, fights ventilator|
|+1 Restless||Anxious, but movements not aggressive|
|0 Alert and Calm|
|–1 Drowsy||Not fully alert, but has sustained awakening (eye opening, eye contact to voice >10 seconds)|
|–2 Light sedation||Briefly awakens with eye contact to voice (<10 seconds)|
|–3 Moderate sedation||Movement and eye opening but no eye contact|
|–4 Deep sedation||No response to voice, but movement or eye opening to physical stimulation|
|–5 Unarousable||No response to voice or physical stimulation|
|Nursing Instrument for Communication of Sedation (NICS) [Reference Mirski, LeDroux and Lewin9]|
|+3 Dangerously agitated||Physical risk to patient or others|
|+2 Agitated||Frequent or constant motor activity requiring restraints not controlled with verbal reminders|
|+1 Anxious, fidgety||Calms with reassurances and instruction|
|0 Awake, cooperative, calm|
|–1 Lethargic||Arouses easily to voice or gentle tactile stimulation|
Attentive, purposeful stimulation motor examination, eyes closed when not stimulated
|–2 Deeply sedated||Requires loud voice or deep stimulation to arouse|
Will follow commands briefly only when stimulated
|–3 Unresponsive||No command-following or purposeful motor activity|
|Riker Sedation-Agitation Scale (SAS)[Reference Jacobi, Fraser and Coursin8]|
|7 Dangerous agitation||Pulling at endotracheal tube (ETT), trying to remove catheters, climbing over bed rail, striking at staff, thrashing side-to-side|
|6 Very agitated||Does not calm despite frequent verbal reminding of limits, requires physical restraints, biting ETT|
|5 Agitated||Anxious or mildly agitated, attempts to sit up, calms down to verbal instructions|
|4 Calm and cooperative||Calm, awakens easily, follows commands|
|3 Sedated||Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands|
|2 Very sedated||Arouses to physical stimuli, but does not communicate or follow commands, may move spontaneously|
|1 Unarousable||Minimal or no response to noxious stimuli, does not communicate or follow commands|
|Motor Activity Assessment Scale (MAAS) [Reference Jacobi, Fraser and Coursin8]|
|6 Dangerously agitated||No external stimulus is required to elicit movement and patient is uncooperative, pulling at tubes or catheters or thrashing side-to-side or striking at staff or trying to climb out of bed and does not calm down when asked|
|5 Agitated||No external stimulus is required to elicit movement and attempting to sit up or moves limbs out of bed and does not consistently follow commands (e.g. will lie down when asked but soon reverts back to attempts to sit up or move limbs out of bed)|
|4 Restless and cooperative||No external stimulus is required to elicit movement and patient is picking at sheets or tubes or uncovering self and follows commands|
|3 Calm and cooperative||No external stimulus is required to elicit movement and patient is adjusting sheets or clothes purposefully and follows commands|
|2 Responsive to touch or name||Opens eyes or raises eyebrows or turns head toward stimulus or moves limbs when touched or name is loudly spoken|
|1 Responsive only to noxious|
|Opens eyes or raises eyebrows or turns head toward stimulus or moves limbs with noxious stimulus|
|0 Unresponsive||Does not move with noxious stimulus|
|Ramsay Scale[Reference Jacobi, Fraser and Coursin8]|
|1||Patient anxious and agitated or restless or both|
|2||Patient cooperative, oriented and tranquil|
|3||Patient responds to commands only|
|4||A brisk response to a light glabellar tap or loud auditory stimulus|
|5||A sluggish response to a light glabellar tap or loud auditory stimulus|
|6||No response to a light glabellar tap or loud auditory stimulus|
|AVRIPAS – Revised Sedation Scale [Reference Avripas, Smythe and Carr13]|
|1||Unresponsive to command/difficult to arouse, eyes remain closed, physical stimulation|
|2||Appropriate response to physical/mostly sleeping, eyes closed to stimuli, calm|
|3||Mild anxiety, delirium, agitation/dozing intermittently, arouses easily (calms easily)|
|4||Moderate anxiety, delirium, agitation/awake, calm.|
|5||Severe anxiety, delirium, agitation/wide awake, hyperalert|
|1||Intubated, no spontaneous effort|
|2||Respirations even, synchronized with ventilator|
|3||Mild dyspnea/tachypnea, occasional asynchrony|
|4||Frequent dyspnea/tachypnea, ventilator asynchrony|
|5||Sustained, severe dyspnea/tachypnea|
Benzodiazepines and propofol are commonly administered sedative agents in the neuro-ICU [Reference Makii, Mirski and Lewin5,Reference Mirski and Hemstreet6,Reference Hutchens, Memtsoudis and Sadovnikoff10,Reference Young and Prielipp11].
Mechanism of action: interact at specific binding site on neuronal γ-aminobutyric acid A (GABAA) receptors that contain specific α-subunits [Reference Fraser, Devlin and Worby12]
Possess sedative, hypnotic, but lack intrinsic analgesic benefits
Potentiate effects of narcotics when given together
Induce anterograde amnesia, not retrograde
In addition to their sedative and anxiolytic effect, benzodiazepines (BZs) have other central nervous system (CNS) advantages, such as anticonvulsant, decreasing cerebral blood flow (CBF), decreasing cerebral metabolic rate of oxygen demand (CMRO2), no change in intracranial pressure (ICP), and central muscle relaxation
Onset of action: 5 minutes
Elimination half-life: 60 minutes
Duration of action: 0.5–3.5 hours
May require continuous infusion or alternative airway support
Precipitates withdrawal in benzodiazepine-dependent patients
May precipitate seizures or status epilepticus
With prolonged use: tachyphylaxis, reversible encephalopathy
Withdrawal syndrome, possible seizures on acute cessation
Paradoxical reactions causing increased agitation and delirium in patients with pre-existing CNS pathology can occur due to altered sensory perception
Decreases tidal volume, compensated by increase in respiratory rate
Blunts response to hypoxia and hypercarbia [Reference Young and Prielipp11].
Most commonly used BZ in the ICU for sedation and also the drug of choice for acute and short-term sedation; three to four times more potent than diazepam, shortest half-life of all BZs, no significant active metabolites, water soluble [Reference Makii, Mirski and Lewin5,Reference Mirski and Hemstreet6,Reference Young and Prielipp11]
Highly lipophilic; therefore, crosses the blood–brain barrier quickly, resulting in a rapid onset of action, 2–5 minutes
Prescribed dose for maintenance of sedation in critically ill adult patients: 2–5 mg/h (0.02–0.1 mg/kg/h)
Short duration of action (2–6 hours) due to rapid metabolism by the liver to an inactive metabolite
Distribution half-life: 7–10 minutes
Elimination half-life: 2–2.5 hours
Half-life (time for drug plasma concentration to decrease by 50% after cessation of a continuous infusion) depends on infusion duration.
Table 5.1 lists commonly used scales for assessment of sedation in the intensive care unit (ICU).
Elderly and patients with liver disease: increased volume of distribution and decreased elimination
Increased effect in patients with renal failure due to increase in active unbound portion
Repeated doses or continuous IV can lead to prolonged sedation despite its short half-life, due to sequestration in fat stores and its slower release from these stores later. Respiratory and cardiovascular depression are minimal with continuous infusion due to lower peak plasma concentration than with bolus dosing [Reference Young and Prielipp11].
Slower onset of action, 5–10 minutes due to lower lipid solubility; therefore, less appealing for acute agitation
Prescribed dose: 0.044 mg/kg every 2–4 hours; infusion rates up to 10 mg/h safe and effective in ICU patients
Greater water solubility, which prolongs its serum half-life:
Distribution half-life: 3–10 minutes
Elimination half-life: 10–20 hours
No active metabolite; therefore resistant to drug interactions except valproic acid, which inhibits lorazepam metabolism
Lorazepam is carried in a solvent solution (propylene glycol) to increase its solubility in the plasma. Excess doses of lorazepam infusion may lead to propylene glycol toxicity. Propylene glycol is converted in the liver to lactic acid. Toxicity is characterized by lactic acidosis, delirium, hallucinations, hypotension, and in severe cases multiorgan failure. This toxidrome has been reported in patients receiving high doses of intravenous lorazepam for more than two days. Thus, an unexplained metabolic acidosis in patients receiving high-dose lorazepam for more than 24 hours must bring attention to this complication [Reference Young and Prielipp11].
Prescribed dose: 0.1–0.2 mg/kg every 2–4 hours
Distribution half life: 50–120 minutes
Elimination half-life: 20–40 hours. Active metabolite, desmethyl-diazepam, with elimination half-life of 96 hours, results in accumulation of both the parent diazepam and metabolite with repeated doses; further converted to oxazepam (t1/2 = 10 hours)
This BZ has a long half-life due to its potent active metabolites, which limits its use in the ICU, where a titratable short-acting drug with rapid reversal of effect is often required
Resedation occurs after reversal with flumazenil because of its long duration of action
Formulated in sterile fat emulsion (previously in propylene glycol), which has reduced complications (thrombophlebitis, thrombosis, metabolic acidosis)
Minimal cardiovascular depressant effects on blood pressure and respiratory drive [Reference Young and Prielipp11].
BZs may be used synergistically with other drugs to lower the side effect profile and decrease toxicity. Examples include the combination of haloperidol and BZ. In this case, lower doses of BZ and haloperidol may result in lower risk of impaired respiratory drive and decreased risk of extrapyramidal symptoms, respectively.
Another example is the combination of propofol and BZ. This combination may result in better hemodynamic stability due to lowering the dose of propofol [Reference Mirski and Hemstreet6,Reference Young and Prielipp11].
Mechanism of action: enhances γ-aminobutyric acid (GABA) transmission; antagonist at N-methyl-d-aspartate (NMDA) receptors. Its GABA receptor site is different from the BZ GABA site [Reference Angelini, Ketzler and Coursin14].
Pure sedative-hypnotic, little analgesic action, some antegrade amnesia
Usual dosage in the ICU is 1–3 mg/kg/h
Produces general anesthesia at induction dose of 2 mg/kg
Onset of action: 1–2 minutes
Ultra-short-acting due to:
Highly lipophilic structure and extensive tissue redistribution
After cessation of continuous infusion, recovery from unconsciousness to awake, responsive state occurs within 10–15 minutes without withdrawal or tolerance; more reliable weaning from mechanical ventilation than midazolam infusion.
Predictable kinetics, even in the presence of hepatic and renal failure
Distribution half-life: 2–4 minutes
Elimination half-life: 30–60 minutes
Terminal half-life, during which propofol is eliminated from tissue fat, 300–700 minutes
Hemodynamic effects: decreases all cardiac indices including: mean arterial pressure (MAP), systemic vascular resistance (SVR), central venous pressure (CVP), cardiac output (CO) and heart rate (HR).
CNS effects: decreases ICP, CMRO2, and potentially cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) because of its effects on MAP. Thus, pressors are often required to maintain CPP. However, this effect is rarely seen with the lower infusion doses used for sedation. This effect on ICP makes it a good treatment option in patients with elevated ICP. It also may be used for treatment of status epilepticus. Its role as a neuroprotective agent, found in animals, has not been well demonstrated in human studies [Reference Hutchens, Memtsoudis and Sadovnikoff10].
Given its short half-life, titrability, and quick systemic clearance, it is an appealing sedative agent in the neuro-ICU, especially in mechanically ventilated patients [Reference Hutchens, Memtsoudis and Sadovnikoff10].
There is a spectrum of abnormal movements associated with peri-operative propofol infusion, including myoclonus, seizure-like events, and possibly seizures. Propofol at low doses or at the beginning of infusion may have potential pro-convulsant activity [Reference Makii, Mirski and Lewin5,Reference Mirski and Hemstreet6].
Hypotension, especially in hypovolemic patients; however, better cardiovascular stability compared with barbiturate therapy
Respiratory depressant: infusions increase respiratory rate and reduce ventilation response to hypercarbia, impair upper airway reflexes, bronchodilator effects in patients with reactive airways disease, increases CO2 production – requires increased minute ventilation to maintain normal acid–base status
Hypertriglyceridemia and pancreatitis because it is mixed as an emulsion in a phospholipid vehicle
Potential for infection and drug incompatibility requiring a dedicated IV catheter
Pain with peripheral injection necessitating central access; consider lidocaine before administration
Tonic–clonic seizures when abruptly stopped after days of infusion
Rarely, urine, hair, and nail beds turn green [Reference Hutchens, Memtsoudis and Sadovnikoff10].
Syndrome of metabolic acidosis, rhabdomyolysis, elevated creatine kinase (CK), renal failure, myocardial failure, cardiac arrhythmias, and hyperlipidemia [Reference Angelini, Ketzler and Coursin14–Reference Zarovnaya, Jobst and Harris16]
Pathogenesis related to propofol-induced blockade of mitochondrial fatty oxidation and accumulation of free fatty acids with pro-arrhythmic effects
Most cases reported in children, resulting in part from reduced energy stores and higher sympathetic tone
Approximately 20 adult cases reported, usually in settings of head injury or other brain injury, including status epilepticus
Mortality is about 30%
Recommended to avoid prolonged propofol infusion (>48 hours) at rates >5 mg/kg/h in adults
Patients on long-term propofol infusions (>72 hours) should be monitored for signs of this syndrome, including elevated CK, hypertriglyceridemia, and liver profile [Reference Hutchens, Memtsoudis and Sadovnikoff10].
Mechanism of action: highly selective α2-adrenergic agonist, decreases sympathetic activity [Reference Mirski and Hemstreet6]
It has unique properties by providing sedation and analgesia without affecting the arousal system as BZs and propofol do. The electroencephalogram (EEG) pattern of these patients is similar to sleep EEG. Thus, patients can be deeply sedated, but they still arouse well. Dexmedetomidine does not have amnestic effect and it does not cause respiratory depression. It is an appealing agent for the neuro-ICU as it facilitates neurologic exams without clinically significant changes in ICP or CPP.
Recommended for short-term sedation <24 hours
Decrease in ICP reported in experimental studies and may be due to α2-receptor-induced arteriolar vasoconstriction causing decreased CBV
Usual dosage: load at 0.1 μg/kg IV for 10 minutes, then 0.2–0.7 μg/kg per hour; avoid bolus dose to minimize hypotension
Elimination half-life: 2 hours; duration of action: 2–6 hours
Route of elimination: 95% renal
Side effects: hypotension and bradycardia, agitation
Multicenter studies revealed that dexmedetomidine recipients required no additional supplements for sedation; however, due to lack of amnestic properties, benzodiazepines and narcotics may be required to improve amnesia and analgesia. Compared to midazolam, dexmedetomidine is associated with a lower risk of delirium, hypotension and decreased mechanical ventilation times [Reference Mirski and Hemstreet6]. Dexmedetomidine also has the potential to become a novel therapeutic option for the management of alcohol withdrawal syndrome-associated agitation and autonomic hyper-reactivity and may reduce benzodiazepine requirements and improve the hemodynamic profile and alcohol withdrawal severity [Reference Mueller, Preslaski and Kiser17]. Further study is required to answer this clinical question. Overall, dexmedetomidine appears to be a good sedative agent in the neuro-ICU [Reference Aryan, Box, Ibrahim, Desiraju and Ames18]. However, at this time its high price limits its use to selected cases.
Mechanism of action: central α2-agonist
Uses: sedative, analgesic, hypertension, blunt manifestations of substance abuse withdrawal, postoperative shivering
CNS: decreases CBF; decreases CPP, no clear effect on CMRO2
Distribution half-life: 6–14 minutes
Elimination half-life: 7–10 hours
Side effects: sedation, dry mouth, rebound hypertension approximately 18 hours after clonidine is discontinued, decreased MAP
Usual dose: 0.1 mg q8–24h; up to 0.6 mg/day; duration of action: 12–48 hours
Studied as adjuvant to morphine patient-controlled analgesia (PCA): bolus of clonidine at end of operation improved analgesia for first 12 hours postoperatively and addition of clonidine to PCA (20 μg; lockout interval (LI): 5 minutes) significantly reduced nausea and vomiting in females undergoing lower abdominal surgery [Reference Angelini, Ketzler and Coursin14].
Mechanism of action: central postsynaptic dopamine antagonist
It is used mainly for treatment of hallucinations, psychosis and agitation associated with delirium. It does not have analgesic or amnestic properties and it is not recommended as a first-line drug for sedation
Usual dose (for delirium): 1–5 mg increments IV, q hourly; infusions of approximately 300 mg/24 h shown to provide sedation without respiratory depression
Distribution half-life: 5–17 minutes
Elimination half-life: 10–19 hours
Metabolized by liver and excreted by kidneys
Contraindication: allergy to droperidol, Parkinson’s disease, pregnancy, seizures (decreases seizure threshold)
Extrapyramidal symptoms (acute dystonic reaction) treated with diphenhydramine
Hypotension due to α-blocking property
Neuroleptic malignant syndrome (NMS)
Symptoms and signs: hyperthermia, muscle rigidity, autonomic instability, increased creatine phosphokinase (CPK), granulocytosis, hyperglycemia
Pathophysiology: dysautonomia due to dopamine antagonism
Treatment: discontinue the drug and start dantrolene and/or bromocriptine
Haloperidol should be used with caution in neurosurgical conditions or patients with brain injury due to its effects on decreasing seizure threshold [Reference Barr, Fraser and Puntillo7,Reference Fraser, Devlin and Worby12].
Like haloperidol, useful for decreasing anxiety associated with psychosis, but less effective for situational anxiety; antiemetic effect
Usual sedative dose: 0.625–2.5 mg IV q4–24 h; up to 5 mg in 24 hours
Duration of action: 2–12 hours
Mechanism of action: pharmacologically active component is dextroisomer, which produces sedation through stimulation of GABA receptor
Usual dose for induction of anesthesia: 0.3 mg/kg
Elimination half-life: approximately 30 minutes
Metabolized by liver to inactive carboxylic acid ester
CNS: decreases CBF, decreases CMRO2, decreases ICP, increases CPP
CVS: unchanged CO and HR. No initial hypotension, but, it can induce prolonged hypotension due to adrenal suppression
Side effects: nausea, vomiting, thrombophlebitis (due to propylene glycol formulation), generalized seizures, myoclonus, adrenal suppression, increased intraocular pressure
Contraindications: acute intermittent porphyria, seizures
Prolonged infusions for sedation in critically ill patients have been terminated due to increased mortality likely related to adrenal suppression. On the other hand, the use of single-dose etomidate for rapid sequence intubation is controversial, as some studies have linked it to worse outcomes in cases of sepsis and trauma due to adrenal suppression [Reference Vinclair, Broux and Faure20]. Another large retrospective analysis did not find any association with worse outcomes [Reference McPhee, Badawi and Fraser21]. These findings have decreased the use of etomidate for intubation in the ICU [Reference Warner, Cuschieri, Jurkovich and Bulger22].